Patent EA-004139-B1 (EA)
Title: Phenylxanthine derivatives
Inventor: DALUGE SUSAN MARY
IPC: C07D473/06
Filed: 1999-08-11
Abstract: 1. A compound formula (I): wherein Z represents a 5 or 6 membered cycloalkyl, aryl, substituted cycloalkyl, or substituted aryl, said cycloalkyl, aryl, substituted cycloalkyl or substituted aryl optionally containing one or more heteroatoms selected from O, N or S; R<1> represents hydrogen or methyl; R<2> represents hydrogen, C1-12alkyl, aryl, or aralkyl; k represents 0 or 1; n represents an integer of 8 to 20; X represents -O-, -N(H)-, -N(C1-6alkyl)-, -N(C3-8cycloalkyl)-, -N(C1-8alkyl)(C3-8cycloalkyl), -N[(CH2CH2O)m(C1-12alkyl, aryl, or aralkyl)]-, -CH2O-, -CH2NH-, -CH2N(C1-6alkyl)-, -CH2N(C3-8cycloalkyl)-, or -C1-12alkyl-; m represents 0-12; Q represents (-CH2)p, (-CH=CH-)p, (-C [triple bond] C-)p, (-(O)p<1>,CH2-)p or (-CH2(O)p<1>)p where p and p<1> independently represent an integer of from 0 to 4; y and y' independently represent integers from 0 to 10; R<3> represents H, straight or branched C1-12alkyl (optionally substituted by phenyl, -CO- phenyl, CN, -CO(C1-3) alkyl, -CO2(C1-3)alkyl, or containing one or more O atoms in the alkyl chain); C1-6 straight or branched alkenyl, C1-6 straight or branched alkynyl or a group -C1-3alkyl -NR<8>R<9>; wherein R<8> and R<9> are independently H, C1-3alkyl or together form a 5 or 6 membered heterocyclic group, optionally containing other heteroatoms selected from O, N or S; R<4> and R<5> independently represent -C3-8 cycloalkyl, -straight chain or branched C1-6alkyl, -hydrogen, -straight chain or branched C2-6alkenyl, -aryl or substituted aryl; -heterocyclic group or substituted heterocyclic group, including heteroaryl and substituted heteroaryl groups; R<6> and R<7> independently represent O or S; with the proviso that when -y and y' both represent 1, -k represents 1, -p<1> represents zero, -R<2> represents H or Me, -R<3> represents H, -X represents O or NH, and -Z represents phenyl, R<4> and R<5> do not both represent cyclohexyl; or a solvate thereof. 2. A compound formula (Ia): wherein Z represents a 5 or 6 membered cycloalkyl, aryl, substituted cycloalkyl, or substituted aryl, said cycloalkyl, aryl, substituted cycloalkyl or substituted aryl optionally containing one or more heteroatoms selected from O, N or S; R<1> represents hydrogen or methyl; R<2> represents hydrogen, C1-12alkyl, aryl, or aralkyl; k represents 0 or 1; n represents an integer of 8 to 20; X represents -O-, -N(H)-, -N(C1-6alkyl)-, -N(C3-8cycloalkyl)-, N[(CH2CH2 O)m(C1-12alkyl, aryl, or aralkyl)]-, -CH2O-, -CH2NH-, -CH2N(C1-6alkyl)-, -CH2N(C3-8cycloalkyl)-, or -C1-12alkyl- m represents 0-12; Q represents (-CH2)p, (-CH=CH-)p, (-C [triple bond] C-)p, (-(O)p<1> CH2-)p or (-CH2(O)p<1>)p where p and p<1> independently represent an integer of from 0 to 4; y and y' independently represent integers from 0 to 10; R<3> represents H, straight chain or branched C1-12alkyl (optionally substituted by phenyl, -CO- phenyl, CN, -CO(C1-3) alkyl, -CO2(C1-3)alkyl, or containing one or more O atoms in the alkyl chain); C1-6 straight or branched alkenyl, C1-6 straight or branched alkynyl or a group -C1-3alkyl -NR<8>R<9>, wherein R<8> and R<9> are independently H, C1-3alkyl or together form a 5 or 6 membered heterocyclic group, optionally containing other heteroatoms selected from O, N or S; R<4> and R<5> independently represent -C3-8cycloalkyl, -straight chain or branched C1-6alkyl, -hydrogen, -straight chain or branched C2-6alkenyl, -aryl or substituted aryl, or -heterocyclic group or substituted heterocyclic group, including heteroaryl and substituted heteroaryl groups; R<6> and R<7> independently represent O or S; with the proviso that when -y and y' both represent 1, -k represents 1, -p<1> represents zero, -R<3> represents H, -X represents O or NH, and -Z represents phenyl, R<4> and R<5> do not both represent cyclohexyl; or a solvate thereof. 3. A compound as in claims 1 or 2 wherein R<3> represents C1-3alkyl-NR<8>R<9>. 4. A compound according to claims 1 or 2, where Z represents a phenyl ring, thiophene ring or pyridine ring. 5. A compound according to claim 4 where Z represents a phenyl ring. 6. A compound according to claim 5 where the grouping is attached to the phenyl ring in the para position. 7. A compound according to any of claims 1-6 where R<1> is H. 8. A compound according to any of claims 1-7 where R<2> is methyl or ethyl. 9. A compound according to any of claims 1-8 where k is 1. 10. A compound according to claim 9 where n is from 8-15. 11. A compound according to any of claims 1-10 where X is -O-, -N(H)-, or -N(CH3)-. 12. A compound according to any preceding claim where Q is (-CH=CH-)p. 13. A compound according to claim 12 where p represents 1. 14. A compound according to any preceding claim where R<3> is methyl. 15. A compound according to any preceding claim where y and y' are the same. 16. A compound according to claim 15 where y and y' are 1. 17. A compound according to any preceding claim where R<4> and R<5> are independently selected from C1-6alkyl, C3-8cycloalkyl and aryl. 18. A compound according to claim 17, where R<4> and R<5> are independently selected from cyclobutyl, cyclopentyl, cyclohexyl, propyl, butyl, isopropyl, isobutyl and phenyl. 19. A compound according to claim 17 or 18 where R<4> and R<5> are the same. 20. A compound according to any preceding claim where R<6> and R<7> are the same. 21. A compound according to claim 20 where R<6> and R<7> are O. 22. A compound according to claims 1 or 2 where X is -O- and R<1> is H. 23. A compound according to claim 1 which is (E)-4-(1,3-bis(benzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclopentylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclopropylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-[1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]cinnamic acid nonaethylene glycol methyl ether ester; (E)-3-((1-propyl-3-benzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cycloheptylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclohexylethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(phenyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(2-methyl-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-((1-propyl-3-cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(bicyclo(2.2.1)hept-2-ylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1-cyclohexylmethyl-3-butyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-((1-cyclohexylmethyl-3-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(benzyl)-1,2,3,6-tetrahydro-2-thioxo-6-oxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1-methyl-3-(3-cyanobenzyl))-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-((1,3-bis(3-fluorobenzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-((1,3-bis(2-fluorobenzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-((1,3-bisphenethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-((1-cyclohexylmethyl-3-methyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-((1-H-3-(2-methyl-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(4-fluorobenzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid hexaethylene glycol dodecyl ether ester; (E)-4-(1,3-bis(cyclobutylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1-methyl-3-cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1-methyl-3-isobutyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclohexyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclopentylmethyl)-1,2,3,6-tetrahydro-6-oxo-2-thioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether amide; (E)-4-(1,3-bis(2-methyl-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether amide; (E)-4-((1-cyclohexylmethyl-3-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether amide; (E)-4-(1,3-bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-benzyl-1H-purin- 8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-oxo-2-phenylethyl)-1H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin- 8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-propynyl)-1H-purin-8-yl)cinnamic acid nonaethylene glycol methyl ether ester; (E)-4-(1,3-bis(cyclohexylmethyl)-2,3,6,7-tetra